TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is now the most common form of HF and has been reported to be closely related to diabetes. Accumulating evidence suggests that HFpEF patients exhibit cardiac fibrosis. This study investigates whether direct targeted inhibition of the activation of cardiac fibroblasts (CFs), the main effector cells in cardiac fibrosis, improves diabetes-induced HFpEF and elucidates the underlying mechanisms. Twenty-week-old db/db mice exhibited HFpEF, as confirmed by echocardiography and hemodynamic measurements. Proteomics was performed on CFs isolated from the hearts of 20-week-old C57BL/6 and db/db mice. Bioinformatic prediction was used to identify target proteins. Experimental validation was performed in both high glucose (HG)-treated neonatal mouse CFs (NMCFs) and diabetic hearts. TAX1 binding protein 1 (TAX1BP1) was identified as the most significantly differentially expressed protein between 20-week-old C57BL/6 and db/db mice. TAX1BP1 mRNA and protein were markedly downregulated in CFs from diabetic hearts and HG-cultured NMCFs. Overexpression of TAX1BP1 profoundly inhibited HG/diabetes-induced NF-κB nuclear translocation and collagen synthesis in CFs, improved cardiac fibrosis, hypertrophy, inflammation and HFpEF in diabetic mice. Mechanistically, signal transducer and activator of transcription 3 (STAT3), which is phosphorylated and translocated from the cytoplasm into the nucleus under hyperglycemic conditions, bound to TAX1BP1 promoter and blocked TAX1BP1 transcriptional activity, consequently promoting NF-κB nuclear translocation and collagen synthesis in CFs, aggravating cardiac fibrosis, hypertrophy and inflammation, leading to HFpEF in db/db mice. Taken together, our findings demonstrate that targeting regulation of STAT3-TAX1BP1-NF-κB signaling in CFs may be a promising therapeutic approach for diabetes-induced HFpEF.

Complete chloroplast genome sequence and phylogenetic analysis of Clerodendrum japonicum (Thunb.) Sweet (Ajugoideae, Lamiaceae).

Clerodendrum japonicum (Thunb.) Sweet belongs to the genus Clerodendrum in the family Lamiaceae. It is an important medicinal plant with great ornamental and economic value. We sequenced and analyzed the complete chloroplast genome of C. japonicum by Illumina sequencing in this study. The full length of the complete chloroplast genome is 152,215 bp, containing a pair of inverted repeat regions of 25,705 bp (IRa and IRb) separated by a large single-copy region (LSC) of 83,491 bp and a small single-copy region (SSC) of 17,314 bp. The C. japonicum chloroplast genome encodes 131 genes, comprising 85 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and 1 pseudogene. This study will be useful for further study on population, phylogenetic, and molecular genetic studies of this medicinal plant.

Complete chloroplast genome sequence and phylogenetic analysis of Torenia fournieri.

Torenia fournieri belongs to the genus Torenia in the family Linderniaceae. The complete chloroplast genome of T. fournieri was sequenced and analyzed by Illumina sequencing in this study. The full length of the complete chloroplast genome is 153,938 bp, containing a pair of inverted repeat regions of 24,805 bp (IRa and IRb) separated by a large single copy region (LSC) of 85,498 bp and a small single copy region (SSC) of 18,830 bp. The T. fournieri chloroplast genome encodes 131 genes, comprising 87 protein-coding genes, 36 tRNA genes, 8 rRNA genes, without pseudogene. Phylogenetic analysis showed that T. fournieri was closely related to T. benthamiana and T. concolor within the genus Torenia in family Linderniaceae.

Core decompression combined with autologous bone marrow stem cells versus core decompression alone for patients with osteonecrosis of the femoral head: A meta-analysis.

BACKGROUND: The efficacy of core decompression plus autologous bone mesenchymal stem cells (BMSCs) for the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to explore the efficacy of core decompression combined with BMSCs for OFNH patients. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane library databases through October 2018 for randomized controlled trials (RCTs) assessing the effect of core decompression combined with BMSCs for OFNH patients. The primary outcome was the visual analog scale (VAS) score at 6 months, 12 months and 24 months. The pooled data were analyzed using Stata 12.0 software. RESULTS: Fourteen studies with 540 patients (core decompression + BMSCs = 275, core decompression alone = 265) were included in our meta-analysis. Compared with the core decompression alone group, the core decompression + BMSCs group showed a significant decrease in the VAS score at 6 months, 12 months and 24 months, and a decrease in the number of hips undergoing total hip arthroplasty (THA), the Western Ontario and McMaster Universities (WOMAC) score and the volume of the postoperative necrotic zone. Core decompression + autologous BMSCs was associated with an increase in HHS postoperatively. No significant difference existed in adverse events. CONCLUSIONS: Compared with core decompression alone in the treatment of ONFH, the combined utilization of core decompression and autologous BMSCs has better pain relief and clinical outcomes and can delay the collapse of the femoral head more effectively.

Molecular characterization of a stress-induced NAC gene, GhSNAC3, from Gossypium hirsutum.

NAC genes, specific to plants, play important roles in plant development as well as in response to biotic and abiotic stresses. Here, a novel gene encoding a NAC domain, named as GhSNAC3, was isolated from upland cotton (Gossypium hirsutum L.). Sequence analyses showed that GhSNAC3 encodes a protein of 346 amino acids with an estimated molecular mass of 38.4 kDa and pI of 8.87. Transient localization assays in onion epidermal cells confirmed GhSNAC3 is a nuclear protein. Transactivation studies using a yeast system revealed that GhSNAC3 functions as a transcription activator. Quantitative real-time polymerase chain reaction analysis indicated that GhSNAC3 was induced by high salinity, drought and abscisic acid treatments. We overexpressed GhSNAC3 in tobacco by using Agrobacterium-mediated transformation. Transgenic lines produced longer primary roots and more fresh weight under salt and drought stresses as compared to wild-type plants. Collectively, our results indicated that overexpression of GhSNAC3 in tobacco can enhance drought and salt tolerances.

Wogonin exacerbates the cytotoxic effect of oxaliplatin by inducing nitrosative stress and autophagy in human gastric cancer cells.

BACKGROUND: Gastric cancer remains one of the leading cause of death in the world. Drug combinations are potential approaches to provide more efficient treatments that minimize side effects. PURPOSE: We investigated the pharmacological effects of the combination of wogonin with oxaliplatin on gastric cancer cells in vitro and in vivo. METHODS AND RESULTS: In the present study, we found that wogonin enhanced the cytotoxicity of oxaliplatin; the drug combination resulted in strong synergistic inhibition of the cell viability in BGC-823 cells and in a zebrafish xenograft model. Interestingly, the combined treatment of wogonin and oxaliplatin modulated the expression of phospho-JNK (Thr183/Tyr185), phospho-ULK1 (Ser555) and the formation of LC3II. Confocal imaging data consistently showed that wogonin exacerbates the oxaliplatin-induced dissipation of the mitochondrial membrane potential (ΔΨm) and formation of peroxynitrite in BGC-823 cells. Moreover, wogonin allows a reduction in oxaliplatin dose when they are combined; therefore, it is a relevant strategy for reducing the side effects of oxaliplatin while achieving the same response. CONCLUSION: These results suggest that wogonin can be a potential therapeutic candidate for enhancing the efficacy of oxaliplatin in gastric cancer treatment.

The correlation between XIAP gene polymorphisms and esophageal squamous cell carcinoma susceptibility and prognosis in a Chinese population.

OBJECTIVE: This study aims to explore the correlation between X-linked inhibitor of apoptosis protein (XIAP) gene polymorphisms (rs8371 and rs9856) with the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC), providing a potential treatment for ESCC. METHOD: A total of 170 ESCC patients (case group) and 191 healthy people (control group) were enrolled in our study. Genotyping was conducted on the basis of the ligase detection reaction (LDR). The expressions of XIAP polymorphisms were detected. The patients were followed up every three months until death or the last follow-up day. The overall survival (OS) and progression free survival (PFS) were recorded by Kaplan-Meier survival curve, and the relationship between XIAP gene polymorphism and risk and prognosis of ESCC was assessed by Cox multivariate analysis. RESULT: TT+CT genotype and T allele frequencies of XIAP rs8371 and rs9856 in the case group were significantly lower compared to those of the control group (all P<0.05), suggesting that TT+CT genotype of XIAP rs8371 and rs9856 was associated with ESCC susceptibility. XIAP rs8371 and rs9856 polymorphisms were associated with tumor node metastasis (TNM) staging, depth of invasion and lymph node metastasis. The OS and PFS of TT+CT genotype carriers of rs8371 were longer than those of CC genotype carriers. Smoking, alcohol, TNM staging, depth of invasion, and lymph node metastasis were significantly associated with the OS and PFS in ESCC patients. Higher TNM staging, depth of invasion, and presence of lymph node metastasis were independent risk factors, while XIAP rs8371 was an independent protective factor for the prognosis of ESCC patients. CONCLUSION: The present study demonstrates that XIAP rs8371 and rs9856 are associated with susceptibility to ESCC, and rs8371 polymorphisms might serve as an indicator for improved clinical efficacy and prognosis of ESCC patients.

A network meta-analysis for efficacy and safety of seven regimens in the treatment of type II diabetes.

The efficacy and safety of seven regimens based on metformin (placebo plus metformin, dapagliflozin plus metformin, vildagliptin plus metformin, saxagliptin plus metformin, empagliflozin plus metformin, exenatide plus metformin and sitagliptin plus metformin) on type 2 diabetes (T2D) were compared based on network meta-analysis. PubMed, Embase and Cochrane Library were applied in the computer-based retrieval process. Randomized controlled trials (RCTs) which were related with the above seven regimens based on metformin in the treatment of T2D were included in this study. Network meta-analysis merged the direct and indirect comparison evidence for the estimation of the weighted mean difference (WMD), odd ratios (ORs) and surface under the cumulative sequencing ranking curve (SUCRA) values. Eight eligible RCTs were applied in this network meta-analysis. The results demonstrated that: in terms of efficacy, the glycated hemoglobin (HbA1c) levels of T2D patients receiving vildagliptin plus metformin were relatively lower when compared with placebo plus metformin (WMD=-1.95, 95%CI=-3.70--0.23); in comparison with exenatide plus metformin, the triglyceride level in T2D patients taking vildagliptin plus metformin remained relatively lower (WMD=-1.36, 95%CI=-2.64--0.01). In terms of safety, the rate of adverse events in patients with T2D who received empagliflozin plus metformin was relatively lower when compared with saxagliptin plus metformin (OR=0.37, 95%CI=0.14-0.98). Furthermore, the SUCRA value of vildagliptin plus metformin was comparatively higher in efficacy, and that the SUCRA value of saxagliptin plus metformin was relatively lower in safety. The efficacy of vildagliptin plus metformin in patients with T2D is relatively better, while the safety of saxagliptin plus metformin in patients with T2D is relatively poorer.

Silencing of IRF3 alleviates chronic neuropathic pain following chronic constriction injury.

Interferon regulatory factor 3 (IRF3) is a member of IRF family which plays an important role in neuronal survival and neuroprotection. However, the role of IRF3 in neuropathic pain remains unclear. Thus, in this study, we investigated the effect of IRF3 on neuropathic pain in a rat chronic constriction injury (CCI) model. Our results showed that IRF3 was up-regulated in the dorsal root ganglion (DRG) in CCI rats. Intrathecal short-hairpin RNA (shRNA)-IRF3 attenuated mechanical allodynia and thermal hyperalgesia in CCI rats, as well as inhibited the production of TNF-α and IL-1ß in the DRG of CCI rats. Furthermore, we revealed that sh-IRF3 greatly suppressed the expression of p-NF-κB p65 and IκBα degradation in the DRG of CCI rats. In conclusion, our data suggest that knockdown of IRF3 may alleviate neuropathic pain by inhibiting the activation of NF-κB signaling pathway. Therefore, IRF3 may provide an important target for the treatment of neuropathic pain.

[Microsurgery treatment with aneurysm on the top of basilar artery].

OBJECTIVE: To explore the efficacy and method of microsurgery for aneurysm on the top of basilar artery. METHODS: The investigators analyzed retrospectively the clinical data of 8 microsurgical patients with aneurysm on the top of basilar artery from May 2007 to September 2010. There were 5 males and 3 females with an average age of 52.6 years old. Six of 8 cases underwent clipping of aneurysm while other 2 patients received superficial temporal artery-radial artery-posterior cerebral artery bypass grafting surgery and clipping of aneurysm. RESULTS: On the basis of GOS (Glasgow outcome score), the postoperative recovery was excellent in 7 patients. And 1 patient suffered insufficiency of oculomotor nerve similarly as preoperatively. CONCLUSION: The surgical procedures for aneurysm of basilar artery are so complicated as to lead to many complications. A wise choice of operative approaches may yield a better outcome.

[MAP based super-resolution method for hyperspectral imagery].

Hyperspectral imagery (HSI) is used in more and more fields, but its low spatial resolution limits its applications severely. The super-resolution algorithm catches more and more eyes but has not been solved well. In this case, the present paper aimed to do the following researches. The relation modeling was constructed between observed HSI of low resolution and target HSI of high resolution. In the modeling, space transformation was implemented by introducing the operator related to endmembers (EMs) of interest. Maximum posterior probability (MAP) algorithm was used to realize the super-resolution (SR) recovery. Experiments show that the proposed SR method has good recovery effect, low computational complexity, robust noise resistance, and can preserve classes of interest.

[Endmember selection algorithm based on linear least square support vector machines].

Endmember (EM) selection is an important prerequisite task for mixed spectral analysis of hyperspectral imagery. In all kinds of EM selection methods, N-FINDR has been a popular one for its full automation and efficient performance. Unfortunately, the implementation of the algorithm needs dimensional reduction in original data, and the algorithm includes innumerable volume calculation. This leads to a low speed of the algorithm and so becomes a limitation to its applications. In the present paper, an improved N-FINDR algorithm was proposed based on linear least square support vector machines (LLSSVM), which is free of dimensional reduction and makes use of distance measure instead of volume evaluation to speed up the algorithm. Additionally, it was also proposed to endow the algorithm with robustness by controlling outliers. Experiments show that the computational load for EM selection using the improved N-FINDR algorithm based on LLSSVM was decreased greatly, and the selection effectiveness and the speed of the proposed algorithm were further improved by outlier removal and the pixel pre-sorting method respectively.